Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy

Feifei Li,1,2,* Zihou Li,2,3,* Xiaodong Jin,1 Yan Liu,1 Pengcheng Zhang,1,2 Ping Li,1 Zheyu Shen,3 Aiguo Wu,3 Weiqiang Chen,1 Qiang Li1 1Institute of Modern Physics, Chinese Academy of Sciences, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Key Laborator...

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Autores principales:	Li FF, Li ZH, Jin XD, Liu Y, Zhang PC, Li P, Shen ZY, Wu AG, Chen WQ, Li Q
Formato:	article
Lenguaje:	EN
Publicado:	Dove Medical Press 2019
Materias:	gadolinium oxide nanocrystal radiosensitization cytostatic autophagy apoptosis oxidative stress Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/69bbc3435aae4a3db5a05cf7335db6b0
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spelling	oai:doaj.org-article:69bbc3435aae4a3db5a05cf7335db6b02021-12-02T05:22:06ZUltra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy1178-2013https://doaj.org/article/69bbc3435aae4a3db5a05cf7335db6b02019-04-01T00:00:00Zhttps://www.dovepress.com/ultra-small-gadolinium-oxide-nanocrystal-sensitization-of-non-small-ce-peer-reviewed-article-IJNhttps://doaj.org/toc/1178-2013Feifei Li,1,2,* Zihou Li,2,3,* Xiaodong Jin,1 Yan Liu,1 Pengcheng Zhang,1,2 Ping Li,1 Zheyu Shen,3 Aiguo Wu,3 Weiqiang Chen,1 Qiang Li1 1Institute of Modern Physics, Chinese Academy of Sciences, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; 2University of Chinese Academy of Sciences, Beijing 100049, China; 3Key Laboratory of Magnetic Materials and Devices, Chinese Academy of Sciences, Division of Functional Materials and Nano Devices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang 315201, China *These authors contributed equally to this work Background: Gadolinium-based nanoparticles (GdNPs) have been used as theranostic sensitizers in clinical radiotherapy studies; however, the biomechanisms underlying the radiosensitizing effects of GdNPs have yet to be determined. In this study, ultra-small gadolinium oxide nanocrystals (GONs) were employed to investigate their radiosensitizing effects and biological mechanisms in non-small-cell lung cancer (NSCLC) cells under X-ray irradiation.Method and materials: GONs were synthesized using polyol method. Hydroxyl radical production, oxidative stress, and clonogenic survival after X-ray irradiation were used to evaluate the radiosensitizing effects of GONs. DNA double-strand breakage, cell cycle phase, and apoptosis and autophagy incidences were investigated in vitro to determine the radiosensitizing biomechanism of GONs under X-ray irradiation.Results: GONs induced hydroxyl radical production and oxidative stress in a dose- and concentration-dependent manner in NSCLC cells after X-ray irradiation. The sensitizer enhancement ratios of GONs ranged between 19.3% and 26.3% for the NSCLC cells under investigation with a 10% survival rate compared with that of the cells treated with irradiation alone. Addition of 3-methyladenine to the cell medium decreased the incidence rate of autophagy and increased cell survival, supporting the idea that the GONs promoted cytostatic autophagy in NSCLC cells under X-ray irradiation.Conclusion: This study examined the biological mechanisms underlying the radiosensitizing effects of GONs on NSCLC cells and presented the first evidence for the radiosensitizing effects of GONs via activation of cytostatic autophagy pathway following X-ray irradiation. Keywords: gadolinium oxide nanocrystal, radiosensitization, cytostatic autophagy, apoptosis, oxidative stressLi FFLi ZHJin XDLiu YZhang PCLi PShen ZYWu AGChen WQLi QDove Medical Pressarticlegadolinium oxide nanocrystalradiosensitizationcytostatic autophagyapoptosisoxidative stressMedicine (General)R5-920ENInternational Journal of Nanomedicine, Vol Volume 14, Pp 2415-2431 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	gadolinium oxide nanocrystal radiosensitization cytostatic autophagy apoptosis oxidative stress Medicine (General) R5-920
spellingShingle	gadolinium oxide nanocrystal radiosensitization cytostatic autophagy apoptosis oxidative stress Medicine (General) R5-920 Li FF Li ZH Jin XD Liu Y Zhang PC Li P Shen ZY Wu AG Chen WQ Li Q Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy
description	Feifei Li,1,2,* Zihou Li,2,3,* Xiaodong Jin,1 Yan Liu,1 Pengcheng Zhang,1,2 Ping Li,1 Zheyu Shen,3 Aiguo Wu,3 Weiqiang Chen,1 Qiang Li1 1Institute of Modern Physics, Chinese Academy of Sciences, Key Laboratory of Heavy Ion Radiation Biology and Medicine of Chinese Academy of Sciences, Key Laboratory of Basic Research on Heavy Ion Radiation Application in Medicine, Gansu Province, Lanzhou 730000, China; 2University of Chinese Academy of Sciences, Beijing 100049, China; 3Key Laboratory of Magnetic Materials and Devices, Chinese Academy of Sciences, Division of Functional Materials and Nano Devices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang 315201, China *These authors contributed equally to this work Background: Gadolinium-based nanoparticles (GdNPs) have been used as theranostic sensitizers in clinical radiotherapy studies; however, the biomechanisms underlying the radiosensitizing effects of GdNPs have yet to be determined. In this study, ultra-small gadolinium oxide nanocrystals (GONs) were employed to investigate their radiosensitizing effects and biological mechanisms in non-small-cell lung cancer (NSCLC) cells under X-ray irradiation.Method and materials: GONs were synthesized using polyol method. Hydroxyl radical production, oxidative stress, and clonogenic survival after X-ray irradiation were used to evaluate the radiosensitizing effects of GONs. DNA double-strand breakage, cell cycle phase, and apoptosis and autophagy incidences were investigated in vitro to determine the radiosensitizing biomechanism of GONs under X-ray irradiation.Results: GONs induced hydroxyl radical production and oxidative stress in a dose- and concentration-dependent manner in NSCLC cells after X-ray irradiation. The sensitizer enhancement ratios of GONs ranged between 19.3% and 26.3% for the NSCLC cells under investigation with a 10% survival rate compared with that of the cells treated with irradiation alone. Addition of 3-methyladenine to the cell medium decreased the incidence rate of autophagy and increased cell survival, supporting the idea that the GONs promoted cytostatic autophagy in NSCLC cells under X-ray irradiation.Conclusion: This study examined the biological mechanisms underlying the radiosensitizing effects of GONs on NSCLC cells and presented the first evidence for the radiosensitizing effects of GONs via activation of cytostatic autophagy pathway following X-ray irradiation. Keywords: gadolinium oxide nanocrystal, radiosensitization, cytostatic autophagy, apoptosis, oxidative stress
format	article
author	Li FF Li ZH Jin XD Liu Y Zhang PC Li P Shen ZY Wu AG Chen WQ Li Q
author_facet	Li FF Li ZH Jin XD Liu Y Zhang PC Li P Shen ZY Wu AG Chen WQ Li Q
author_sort	Li FF
title	Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy
title_short	Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy
title_full	Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy
title_fullStr	Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy
title_full_unstemmed	Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy
title_sort	ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward x-ray irradiation by promoting cytostatic autophagy
publisher	Dove Medical Press
publishDate	2019
url	https://doaj.org/article/69bbc3435aae4a3db5a05cf7335db6b0
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Ultra-small gadolinium oxide nanocrystal sensitization of non-small-cell lung cancer cells toward X-ray irradiation by promoting cytostatic autophagy

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